DESCRIPTION (adapted from the application) This application for a Mentored Clinical Scientist Development Award (K08) is requested to provide the candidate with five years of mentored career development leading to academic independence. The candidate is an Associate Research Scientist at Yale School of Medicine who has completed more than two years of laboratory training, as well as clinical training in Gastroenterology. The candidate's prior work has focused on regulation of bile secretion and control of cytosolic calcium. In the proposed research project, the candidate will define the functional role of ATP in bile ductular secretion by testing the following specific aims: (1) to identify which P2Y ATP receptors are expressed on bile duct epithelia, (2) to identify the membrane distribution of P2Y ATP receptors which are present on bile duct epithelia, and (3) to determine which P2Y ATP receptors link to bile duct epithelial secretion. The candidate will use this award to develop scientific expertise in regulation of bile ductular secretion, is which will lead to academic independence. The applicant's mentor is an established investigator in second messenger regulation of epithelial secretion, especially as it pertains to the liver, and will support the candidate strongly for the duration of the award. The candidate will have access to state-of-the-art facilities at Yale, as well as opportunities to expand his abilities through appropriate coursework as needed. The Yale School of Medicine Department of Internal Medicine has pledged that the candidate will have extensive protected research time and excellent resources for the duration of the award.